Purpose: The purpose of this study was to evaluate the clinical, pathological, and therapeutic experience of a group of patients with primary oral malignant melanoma (OMM) in Amsterdam, The Netherlands. Patients and Methods: Fourteen patients (5 males, 9 females, mean age 57.9 years) with histopathologic diagnosis of OMM were treated at the Department of Oral and Maxillofacial Surgery/Oral Pathology of the Vrije University Medical Center in Amsterdam between 1978 and 2005. A pigmented, flat or swollen, irregularly bordered lesion of oral mucosa was detected in most patients during the first clinical examination. Pain was the most commonly referred symptom; the palate was the most frequently affected subsite. Following the mucosal melanoma microstaging system, all patients staged as stage I (T any N0M0) could be subclassified as microstage II (invasion up to the lamina propria), except for 1 patient microstaged as stage III (deep skeletal tissue invasion into skeletal muscle, bone, or cartilage). Where possible, surgery was the treatment of choice. Postoperative radiotherapy, using fractions of 6 Gy twice a week for a total dose of 30 Gy, was given to 3 patients. Three patients were treated primarily with radiotherapy alone. Results: Five patients developed local recurrence within 4 to 72 months, and 10 patients developed distant metastases within 6 to 78 months. Ten patients died of their disease within an average interval of 40 months, with a range of 12 to 80 months. Of the 10 patients who qualified for evaluation of the 5-year-survival rate, 1 was alive with disease and 2 were alive without evidence of disease, resulting in a 5-year survival rate of 30%. However, all patients died of their disease before the end of the 10-year follow-up period. Conclusion: Our study confirms that OMM is a rare and aggressive malignancy with a low 5-year survival rate. An evidence-based protocol for the best therapeutic approach is not yet available.